The specificity of the influenza virus hemagglutinin for sialic acid containing receptors on host cells is well established to be an important factor in adaptation of influenza to avian and human hosts. In particular, avian and human influenza viruses preferentially recognize different subsets of sialo-glycans that contain sialic acid in 'a2-3' or 'a2-6' linkage to the underlying glycan chain, respectively. Three projects in this program investigate the molecular basis of influenza virus virulence and host specificity, for which a detailed analysis of the receptor specificity is warranted. Project 1 (Wilson) seeks to understand amino acid changes in the receptor pockets of various hemagglutinin serotypes that confer the classic avian and human type receptor specificity. Project 3 (Garcia-Sastre) seeks to understand the roles of HA and NA proteins in reassortant viruses, involving the infection of single cells by viruses with the same or different receptor specificity. Project 4 (Basler/Crowe) seeks to characterize the molecular properties of antigenic escape viruses. Antigenic escape viruses are documented to result in changes in receptor specificity as an alternative mechanism to loss of antibody binding. Thus, each of these projects will benefit from establishing receptor specificity of the mutant, reassortant, or escape viruses to ascertain the role of receptor specificity on the observed phenotype of the HA. To accomplish this, the Receptor Specificity Core will produce a custom glycan array for analysis of influenza virus receptor specificity. The array will comprise a wide range of sialoside sequences that will approximate the diversity of the glycan array developed by the Consortium for Functional Glycomics, which has become a standard for the analysis of influenza virus receptor specificity. The Core will produce the array and analyze the specificity of the viruses submitted for analysis by the three projects. RELEVANCE (See Instructions): The specificity of influenza virus for glycan receptors on host cells is believed to play an important role in adaptation of avian influenza viruses to human hosts. The Receptor Specificity Core will evaluate the specificity of influenza viruses studied in this program to help elucidate the molecular basis for acquisition of human type receptor specificity, and the role of receptor specificity in virulence and host adaptation.